High resolution x-ray measurements of the electron density distribution (EDD) and molecular electrostatic potential (MEP) for some flexible opiate type drugs, studied because of their analgetic activity, will be collected. With the recent development of experimental x-ray methods, it is now possible to obtain from the same experiment, not only the shape of the drug molecule, but also the EDD and MEP, which may be used to predict the relative reactivities. Studies of other biological model compounds show that these electronic factors are now measurable with an accuracy at least equivalent to the best calculations on small molecules. Initially, a selected set of fentanyl derivatives that have various structural characteristics and varying degrees of analgetic activity have been chosen for study. These studies will be used to identify EDD and MEP trends that may be used to predict relative reactivities. Information will also be available concerning both the stereochemical and electronic requirements of the opiate receptor site and to attempt to understand how such small structural modifications may result in radical differences in antipsychotic activity.